The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. This project takes advantage of methodological advances and findings obtained during the last funding period to: 1) define a high temporal resolution, genome-wide, expression profile of regeneration; 2) interrogate the functions of known embryonic signaling pathways in the adult contexts of tissue regeneration and homeostasis, and to carry out a formal comparison of how the mechanisms of regeneration compare to embryogenesis; 3) uncover genes involved in the regeneration of adult organs after amputation; and 4) Initiate comparative studies of regeneration to test the universality of our findings. All three lines of investigation synergize with each other and their integration should provide us with a high-resolution set of molecular processes regulating regeneration and regenerative capacities. Thus far, this approach has led us to uncover novel animal cell biology and functions in adult contexts of known genes, and to define functions for the many conserved animal genes for which functions are still unknown. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health.

Public Health Relevance

The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM057260-18
Application #
9066688
Study Section
Special Emphasis Panel (NSS)
Program Officer
Haynes, Susan R
Project Start
1998-05-01
Project End
2019-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
18
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Stowers Institute for Medical Research
Department
Type
DUNS #
614653652
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Cheng, Li-Chun; Alvarado, Alejandro Sánchez (2018) Whole-Mount BrdU Staining with Fluorescence In Situ Hybridization in Planarians. Methods Mol Biol 1774:423-434
Merryman, M Shane; Alvarado, Alejandro Sánchez; Jenkin, James C (2018) Culturing Planarians in the Laboratory. Methods Mol Biol 1774:241-258
Sánchez Alvarado, Alejandro (2018) To solve old problems, study new research organisms. Dev Biol 433:111-114
Cheng, Li-Chun; Tu, Kimberly C; Seidel, Chris W et al. (2018) Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea. Dev Biol 433:357-373
Elliott, Sarah A; Alvarado, Alejandro Sánchez (2018) Planarians and the History of Animal Regeneration: Paradigm Shifts and Key Concepts in Biology. Methods Mol Biol 1774:207-239
Adler, Carolyn E; Sánchez Alvarado, Alejandro (2017) PHRED-1 is a divergent neurexin-1 homolog that organizes muscle fibers and patterns organs during regeneration. Dev Biol 427:165-175
Davies, Erin L; Lei, Kai; Seidel, Christopher W et al. (2017) Embryonic origin of adult stem cells required for tissue homeostasis and regeneration. Elife 6:
Sasidharan, Vidyanand; Marepally, Srujan; Elliott, Sarah A et al. (2017) The miR-124 family of microRNAs is crucial for regeneration of the brain and visual system in the planarian Schmidtea mediterranea. Development 144:3211-3223
Ross, Eric; Blair, David; Guerrero-Hernández, Carlos et al. (2016) Comparative and Transcriptome Analyses Uncover Key Aspects of Coding- and Long Noncoding RNAs in Flatworm Mitochondrial Genomes. G3 (Bethesda) 6:1191-200
Lei, Kai; Thi-Kim Vu, Hanh; Mohan, Ryan D et al. (2016) Egf Signaling Directs Neoblast Repopulation by Regulating Asymmetric Cell Division in Planarians. Dev Cell 38:413-29

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